A new mutation in the beta-globin gene (IVS II-850 G-C) found in a Yugoslavian beta-thalassemia heterozygote

The recent development of laboratory techniques that can rapidly characterize the molecular defects of beta-thalassemia has resulted in the discovery of more than 100 different point mutations in the beta-globin gene. These mutations are population specific. About 20 of them account for over 90% of...

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Bibliographic Details
Published inHaematologica (Roma) Vol. 77; no. 2; p. 119
Main Authors Jankovic, L, Dimovski, A J, Sukarova, E, Juricic, D, Efremov, G D
Format Journal Article
LanguageEnglish
Published Italy 01.03.1992
Subjects
Base Sequence
Blotting, Northern
Globins - genetics
Heterozygote
Humans
Molecular Sequence Data
Mutation
Polymerase Chain Reaction
RNA Splicing
Thalassemia - blood
Thalassemia - genetics
Yugoslavia
Yugoslavia
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Summary:The recent development of laboratory techniques that can rapidly characterize the molecular defects of beta-thalassemia has resulted in the discovery of more than 100 different point mutations in the beta-globin gene. These mutations are population specific. About 20 of them account for over 90% of beta-thal genes in the world. The other mutations are usually found in single families. In this paper we describe a case with a novel mutation at position IVS II-850 (G-C) as a cause of beta-thalassemia. Direct sequencing of PCR amplified DNA was used for the detection of the mutation. ASO probes were synthesized for dot-blot hybridization. Expression of the mutated allele was evaluated through Northern blot and RNA-PCR analyses. This mutation was found in four members of a family, who exhibited severe microcytosis and hypochromic anemia, with an average alpha/beta ratio of 2.0. The sequencing of PCR amplified DNA showed a G-C mutation at position IVS II-850 of the beta-globin gene. Dot blot analyses confirmed the presence of this substitution in all four carriers. Northern blot and RNA-PCR analyses did not reveal any abnormally spliced mRNA species. The G-C substitution at position IVS II-850 is the third mutation in the invariant AG dinucleotide of the acceptor splice site of the second intron of the beta-globin gene. It abolishes normal splicing, which leads to abnormally processed mRNA. It is a relatively rare mutation since it was not detected among the uncharacterized beta-thal chromosomes from Yugoslavia.
ISSN:0390-6078